Ongoing studies of the enzyme aryl hydrocarbon hydroxylase (AHH) have been applied to a small series of subjects with large bowel cancer. This enzyme is known to convert certain polycyclic hydrocarbon carinogens to their active molecule, and is studied in human subjects utilizing short-term cultured lymphocytes as a tissue source. We have previously demonstrated genetic variation in the activity of this enzyme. Results with the large bowel cancer subjects indicates no difference from the normal population, but the series is too small for significance, particularly in terms of studying the several types and locations of large bowel tumor. The series will be extended. Meanwhile, major effort this past year has been on improvement and stardardization of the assay, with considerable success. Methods for study of other carcinogen-metabolizing enzymes have been developed, based on the principle of formation of metabolites which are actively mutagenic and detectable in bacterial test systems. With this method we have advanced the understanding of metabolism and active metabolites of the carcinogen aminoacetyl-fluorene (AAF), have demonstrated the active molecule to be nitrosofluorene and have discovered a new enzyme in rat tissues which is in the soluble cell fraction. These studies are being extended to human material. Another bacterial test system has been developed which utilizes direct action of the metabolite on purified bacterial DNA, alteration of which is then detected by employing the DNA to demonstrate bacterial transformation. This obviates the problem of possible further metabolism of the carcinogen withint the bacterial cell. BIBLIOGRAPHIC REFERENCES: Shaw, Charles R. The microsomal mixed function oxidases and chemical carcinogens. In Isozymes III, Developmental Biology, ed. C. Markert, Academic Press, New York, pp 809-018, 1975. Shaw, C. R. Genetic variation in carcinogen-metabolizing enzymes. Second Workshop on Large Bowel Cancer Meeting (NCI), (Abtract), 1975.